Abstract 10863: Bone Marrow Mesenchymal Stem Cells Prevent Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia After Arterial Injury in Rats by Altering Smooth Muscle Cell Phenotype
Accumulating evidence from animal studies shows that the administration of mesenchymal stem cells (MSCs) from adult bone marrow ameliorates tissue damage after injury or disease episodes such as myocardial infarction or stroke. However, the therapeutic potential of MSCs in restenosis following vascular injury has been poorly investigated. Hence, we examined whether MSCs prevent neointimal hyperplasia in a rat carotid arterial injury model.
Methods and Results: Sprague-Dawley rats underwent balloon injury to right carotid arteries. Cultured MSCs from GFP-transgenic rats (0.8x 106 cells, n= 10) or vehicle (controls, n= 10) was locally administered from the adventitial site of the injured arteries 2 days after inducing injury. We observed a few GFP-positive cells in the adventitia 3 days after the administration. However, no MSCs differentiated into the endothelial cells or vascular smooth muscle cells (VSMCs) after 14 days. Despite of lack of the vascular cell differentiation, the local MSC administration significantly prevented neointimal hyperplasia (intima/media ratio: 0.94 ± 0.10 in the controls vs. 0.58 ± 0.08 in the MSC group, p< 0.01) and reduced the percentage of Ki67+ proliferating cells (39.8 ± 3.1 vs. 27.8 ± 3.7 %, p< 0.05) in the arterial walls 14 days after the treatment. By immunohistochemistry, neointimal cells in the MSC-treated arteries showed reduced expression of embryonic myosin heavy chain and RM-4, an inflammatory cell marker, compared with neointima of controls. Cultured rat VSMCs were studied to test the hypothesis that MSC-secreted factors inhibited VSMC proliferation. Conditioned medium from MSCs increased p27 protein in VSMCs exposed to platelet derived growth factor (PDGF)-BB and significantly attenuated VSMC proliferation (25% reduction, p< 0.001). The MSC-conditioned medium suppressed the expression of PDGF receptor alpha, RM-4 and inflammatory cytokines in VSMCs treated with PDGF-BB.
Conclusion: Our results suggest that perivascular administration of MSCs may prevent restenosis after vascular intervention. Mechanisms of benefit appear to be attributable to modulation of the inflammatory VSMC phenotype via paracrine effects.
- © 2011 by American Heart Association, Inc.